1. Field of the Invention
The present invention relates to a novel 2-phenyl-2-(2'-piperidinylidene)acetate derivative and a process for manufacturing the same. This derivative is useful as a raw material for manufacturing an optically active 2-phenyl-2-(2'-piperidinyl)acetate derivative which is the major intermediate of an antidepressant as described below. The present invention also relates to a process for manufacturing an optically active 2-phenyl-2-(2'-piperidinyl)acetate derivative which is a major intermediate of an antidepressant.
2. Description of the Related Art
As an antidepressant, methyl threo-2-phenyl-2-(2'-piperidinyl)acetate/hydrochloride (Trade name: Ritalin) is commercially available in the form of racemic compounds. Also, it is known for this antidepressant that a specific stereoisomer has a pharmacological activity five times higher than that of other stereoisomers (see U.S. Pat. No. 2,957,880).
Further structural analysis studies on methyl 2-phenyl-2-(2'-piperidinyl)acetate have progressed and the absolute configuration of the optically active form of this compound has been reported (see J. Med. Chem., 12, 266, 1969).
The above optically active methyl 2-phenyl-2-(2'-piperidinyl)acetate is manufactured, for example, by the following known processes:
(1) A process in which phenylacetonitrile and 2-chloropyridine are condensed in the presence of sodium amide, followed by hydrolysis and a reduction to prepare 2-phenyl-2-(2'-piperidinylidene)acetic acid amide (see U.S. Pat. No. 2,507,361). A threo compound is then prepared by a recrystallization of that acid amide. The threo compound is then optically resolved using optically active tartaric acid, followed by hydrolysis and an esterification reaction to synthesize the above optically active compound (see U.S. Pat. No. 2,957,880). PA1 (2) A process in which optically active chlorophenylamine is subjected to a Hofmann decomposition reaction to prepare an olefinic compound, which is then subjected to an oxidation reaction using ozone to synthesize the above optically active compound (see J. Pharm. Sci, 56, 1689, 1967). PA1 (a) A process in which a protective group for an amino group is removed (hereinafter referred to as "protection removal") from the compound represented by formula (2) and the resulting compound is reacted to combine the carbon atoms at the third position and at the seventh position thereof to produce the compound represented by formula (1); PA1 (b) A process in which the protection removal and the reaction of combining the carbon atoms at the third and the seventh positions of the compound represented by formula (2) progresses simultaneously to produce the compound represented by formula (1) in one step; and PA1 (c) A process in which only the reaction of combining the carbon atoms at the third and the seventh positions of the compound represented by formula (2) is carried out to produce the compound represented by formula (1). PA1 1) Complexes represented by the formula RuXY'(L), wherein X represents a hydrogen atom, halogen atom, or the carboxylic acid derivative residue; X' represents a halogen atom or the carboxylic acid derivative residue; and L represents an optically active phosphine ligand. PA1 2) Complexes represented by the formula RuX(L)Q!Y, wherein X, Y, L and Q are the same as earlier define. PA1 3) Complexes represented by the formula Ru.sub.2 Cl.sub.4 (L).sub.2 !NR.sup.6 R.sup.7 R.sup.8, wherein L ,R.sup.6, R.sup.7, and R.sup.8 are the same as earlier defined. PA1 4) Complexes represented by the general formula IrQ(L)!Y, wherein Y, L and Q are the same as earlier defined. PA1 5) Complexes represented by the general formula RhQ(L)!Y, wherein Y, L, and Q are the same as earlier defined.
However, in these processes, complicated operations are required and it is also necessary to use an expensive reagent for optical resolution and/or to use an optically active compound.